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The Genotype for DPYD Risk Variants in Patients With Colorectal Cancer and the Related Toxicity Management Costs in Clinical Practice
Author(s) -
Toffoli Giuseppe,
Innocenti Federico,
Polesel Jerry,
De Mattia Elena,
Sartor Franca,
Dalle Fratte Chiara,
Ecca Fabrizio,
Dreussi Eva,
Palazzari Elisa,
Guardascione Michela,
Buonadonna Angela,
Foltran Luisa,
Garziera Marica,
Bignucolo Alessia,
Nobili Stefania,
Mini Enrico,
Favaretto Adolfo,
Berretta Massimiliano,
D'Andrea Mario,
De Paoli Antonino,
Roncato Rossana,
Cecchin Erika
Publication year - 2019
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1257
Subject(s) - dpyd , irinotecan , medicine , genotyping , odds ratio , oncology , toxicity , colorectal cancer , confidence interval , genotype , pharmacogenetics , chemotherapy , pharmacology , cancer , biology , genetics , gene
Lack of information on the clinical utility of preemptive DPYD screening before fluoropyrimidine treatment is a major barrier preventing its use in clinical practice. This study aimed to define the association between DPYD variants and fluoropyrimidine‐related toxicity management costs. A cost analysis was conducted on the toxicities experienced by 550 patients with colorectal cancer treated with fluoropyrimidine‐based chemotherapy. Genotyping for DPYD *2A , DPYD *13 , DPYD c. 2846A>T , DPYD ‐HapB3 , and UGT 1A1*28 was done retrospectively and did not affect patients’ treatments. Carriers of at least one DPYD variant experienced higher toxicity management costs (€2,972; 95% confidence interval (CI), €2,456–€3,505) than noncarriers (€825; 95% CI, €785–€864) ( P < 0.0001) and had a higher risk for toxicity requiring hospitalization (odds ratio, 4.14; 95% CI, 1.87–9.14). In patients receiving fluoropyrimidine/irinotecan, the incremental cost between DPYD variant and UGT 1A1*28/*28 carriers and noncarriers was €2,975. This study suggests that the toxicity management costs during fluoropyrimidine‐based therapy are associated with DPYD and UGT 1A1*28 variants and supports the utility of genotyping.